A hard look at FDA’s review of GRAS notices

Abstract

Generally Recognized as Safe (GRAS) substances are exempt from premarket approval; however, the standard of “reasonable certainty of no harm” is the same. In 1997, the voluntary GRAS affirmation process was replaced with the voluntary U.S. Food and Drug Administration (FDA) GRAS notice process. Under the GRAS notice process, pivotal safety data are required to be in the public domain, and consensus of safety among experts is required. FDA issues responses of “FDA has no questions”, “Notice does not provide a basis for a GRAS determination”, or, “At Notifier’s request, FDA ceased to evaluate the notice.” Of 528 notices reviewed, there were 393 “no questions letters”, 17 “insufficient basis letters”, and 84 “cease to evaluate letters”. Of those deemed to be insufficient, most failed to meet the general recognition criteria. Only four raised questions about potential safety, of which three received a no questions letter upon providing more data. Of the 84 withdrawn notices, 22 received a no questions letter upon resubmission. In spite of criticisms, the FDA GRAS notice process is clearly defined, efficient, and cost-effective, and there have been no known public health issues following its implementation.